Neurofeedback modulation of insula activity via MEG-based brain-machine interface: A double-blind randomized controlled crossover trial

Abstract Insula activity has often been linked to pain perception, making it a potential target for therapeutic neuromodulation strategies such as neurofeedback. However, it is not known whether insula activity is under cognitive control and, if so, whether this activity is consequently causally related to pain. Here, we conducted a double-blind randomized controlled crossover trial to test the modulation of insula activity and pain thresholds using neurofeedback training. Nineteen healthy subjects underwent neurofeedback training for upmodulation and downmodulation of right insula activity using our magnetoencephalography (MEG) based brain–machine interface. We observed significant differences in insula activity between the upmodulation and downmodulation training sessions. Furthermore, resting-state insula activity significantly decreased following downmodulation training compared to following upmodulation training. Compared with upmodulation training, downmodulation training was also associated with increased pain thresholds, albeit with no significant interaction effect. These findings show that humans can cognitively modulate insula activity as a potential route to develop therapeutic MEG neurofeedback systems for clinical testing.